Influence of hydrophobic mismatch and palmitoylation on the association of transmembrane α‐helical peptides with detergent‐resistant membranes

FEBS Letters

Rijkers, Dirk T.S¹  Killian, J.Antoinette²  de Kruijff, Ben²  van Duyl, Bianca Y² 

[1] Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Faculty of Pharmacy, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands;Department of Biochemistry of Membranes, CBLE, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands

关键词: Raft;    Sphingolipid;    Cholesterol;    Triton X-100;    Model membrane;    DRM;    detergent-resistant membrane;    TMD;    transmembrane domain;    TX-100;    Triton X-100;    DOPC;    1;    2-dioleoyl-sn-glycero-3-phosphocholine;    SM;    sphingomyelin;    MLV;    multilamellar vesicle;    WALP;    tryptophan-alanine-leucine peptide;    TLC;    thin layer chromatography;    TFE;    trifluoroethanol;   

DOI  :  10.1016/S0014-5793(02)02939-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The aim of this study was to gain insight into the mechanism through which transmembrane proteins are targeted to liquid ordered (L_o) phase domains or rafts. This was investigated by analyzing the Triton X-100 resistance of designed transmembrane peptides in model membranes of 1,2-dioleoyl-sn-glycero-3-phosphocholine, sphingomyelin and cholesterol (1/1/1, molar ratio), which contain both L_o phase domains and fluid bilayers. By using peptides with one or two palmitate chains covalently linked to their N-terminus or with variable hydrophobic lengths, the roles of protein palmitoylation and of mismatch between the transmembrane segment of the protein and the bilayer thickness, respectively, were investigated. The results show that neither hydrophobic matching nor palmitoylation is sufficient for partitioning of peptides into L_o phase domains. It is concluded that the L_o phase itself, due to the tight packing of the lipids, constitutes an unfavorable environment for accommodation of protein transmembrane segments.

【 授权许可】

Unknown